In broadest terms, the research objective is the elucidation of the mechanisms underlying changed sensitivity of the norepinephrine (NE) receptor coupled adenylate cyclase system in the limbic forebrain and in other brain structures with noradrenergic projections resulting from prolonged administration of psychotropic drugs which can either precipitate or alleviate depression in man. We are interested in gaining fuller insight into the regulation of the density of the Beta-subpopulation of NE receptors coupled to adenylate cyclase in limbic forebrain, cortex and cerebellum and in the elucidation of the neurobiological consequences of drug or ECT induced alteration of noradrenergic receptor function for NE related increases in nervous tissue phosphorylation and cyclic AMP dependent phosphorylation of proteins of synaptic membranes in vitro and in vivo. It is our hope that these studies will not only contribute to a better understanding of the molecular pharmacology of psychotropic drugs, when administered on a clinically relevant time basis, and of electroconvulsive treatment (ECT), but may provide a beginning toward a molecular understanding of affective disorders.